Abstract
Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease ≃200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrP(Sc) (where PrP(Sc) is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrP(Sc). The patterns of MHu2MPrP(Sc) and MoPrP(Sc) accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease >500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.
Original language | English (US) |
---|---|
Pages (from-to) | 9936-9940 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 91 |
Issue number | 21 |
DOIs | |
State | Published - Oct 11 1994 |
Keywords
- bovine spongiform encephalopathy
- human growth hormone
- prion propagation
- scrapie
- species barrier